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Aspect pré analytique et intérêt clinique de la détection d'ADN tumoral circulant par PCR digitale en oncologie digestive

Abstract : For several years, circulating tumor DNA (ctDNA) has emerged as a promising biomarker providing relevant information to optimize patient care in oncology. The aim of this thesis was both: (i) to evaluate different preanalytical and analytical conditions (digital PCR (dPCR) mainly) for the detection of this biomarker; (ii) to evaluate the potential clinical interest of this biomarker in digestive oncology. The first part reports 3 works (3 original articles including a national collaboration (Parisian team led by J. lost)). In work no. 1, we have shown the feasibility of ctDNA detection by dPCR directly from the plasma of 43 samples from patients with metastatic colorectal cancer (mCRC). There was no significant difference in the detection rate of circulating KRAS mutations between groups with and without DNA extraction (93% (40/43) versus 88% (38/43), respectively). In work no. 2, we developed a method based on the heparinase addition for the ctDNA detection from 194 heparinized samples of patients followed in oncology. This treatment of samples by heparinase allowed the ctDNA analysis of 117/194 (60%) patients with prior inhibition of dPCR by heparin. Finally, in work no. 3, we compared several ctDNA detection platforms and snowed that dPCR displayed qualitatively and quantitatively comparable detection results with an ultrasensitive platform of E-ice-COLD-PCR for the samples with ctDNA allelic fraction ?.0 4%. The second part reports 3 works (3 original articles) on the clinical interest of the ctDNA detection by dPCR in digestive oncology. We have thus shown that this biomarker had a diagnostic (work no. 4). prognostic (works no. 4 to 6) and predictive response to treatments (work no. 6) interest in patients with pancreatic adenocarcinoma (work no. 4) and mCRC (works no. 5 to 6).
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https://tel.archives-ouvertes.fr/tel-01716414
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Submitted on : Friday, February 23, 2018 - 3:52:24 PM
Last modification on : Thursday, November 28, 2019 - 3:28:43 AM
Long-term archiving on: : Friday, May 25, 2018 - 2:34:43 AM

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  • HAL Id : tel-01716414, version 1

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David Sefrioui. Aspect pré analytique et intérêt clinique de la détection d'ADN tumoral circulant par PCR digitale en oncologie digestive. Sciences agricoles. Normandie Université, 2017. Français. ⟨NNT : 2017NORMR075⟩. ⟨tel-01716414⟩

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